Male Fertility Potential Molecular Mechanisms Revealed by iTRAQ-Based Quantitative Proteomic Analysis of the Epididymis from Wip1−/− Mice

Abstract Proteomics and postgenomic technologies have found growing recent applications in reproductive biology and fertility research. Mice deficient in the wild-type p53-induced phosphatase 1 (WIP1) exhibit defects in reproductive organs. In this study, we aimed to understand how Wip1 deficiency affects spermatogenesis and sperm maturation using the Wip1−/− mouse model and gel-free isobaric tags for relative and absolute quantitation liquid chromatography–tandem mass spectrometry quantitative proteomic analysis of the whole epididymis, including somatic tissue and sperm. A total of 8763 proteins were identified, of which 91 were significantly differentially expressed proteins (DEPs) in Wip1−/− mice. Of note, four reproduction-related DEPs (PRM2, ODF1, PIWIL1, and KLHL10) were confirmed by western blotting. Pathway analysis suggested that the Smac/Diablo-mediated apoptotic pathway and the SERPINA3-mediated inflammatory process may contribute to the atrophy and marked reduction of sperm in the epididymis....